Fms-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30

Although acute myeloid leukemia (AML) with CBFB::MYH11 rearrangement is classified as favorable-risk, approximately 40% of patients experience relapse. We evaluated the prognostic impact of CBFB::MYH11 transcript levels and the optimal timing of allogeneic hematopoietic cell transplantation (allo-HCT) at first complete remission (CR1). A total of 186 patients with CBFB::MYH11-rearranged AML treated with intensive induction chemotherapy were included. CBFB::MYH11 levels after cycles 2 and 3 were strongly correlated (P < 0.001). The post-cycle 2 CBFB::MYH11 transcript level emerged as the strongest prognostic marker for both disease-free survival (DFS) and overall survival (OS), outperforming assessments after cycles 1 or 3. CBFB::MYH11 ≥ 1% after cycle 2 was independently associated with inferior DFS (HR 3.84, P < 0.001) and OS (HR 3.98, P = 0.003). Among patients with post-cycle 2 CBFB::MYH11 ≥ 1.0%, the 3-year DFS and OS were both 91.7% in patients who received allo-HCT at CR1, compared with 47.8% and 72.9%, respectively, in the chemotherapy consolidation group. Multivariate analysis indicated that allo-HCT in CR1 improved 3-year DFS compared with chemotherapy consolidation (HR 0.24; P = 0.023). However, no significant improvement in OS was observed during follow-up. These findings suggest that post-cycle 2 CBFB::MYH11 level ≥1.0% identifies a high-risk subgroup that may benefit from allo-HCT in CR1.

Background:Enterococcal bloodstream infection (EBSI) carries high mortality in hematologic patients, yet no prognostic model tailored to this population exists. Methods:We retrospectively analyzed 192 hematologic patients (≥14 years) with EBSI admitted between 2014 and 2024. Clinical features, microbiology, treatment, and outcomes were assessed. Candidate predictors for 30-day mortality were selected by LASSO and entered into multivariable logistic regression. A simplified risk score was derived from regression coefficients and internally validated by bootstrap resampling. Results:The median patient age was 43 years, and acute leukemia was the predominant underlying disease (72.4%). Enterococcus faecium was the leading pathogen (71.4%), with low vancomycin resistance (1.6%). Most cases (71.9%) occurred as breakthrough infections, mainly during carbapenem therapy, and 72.9% met mucosal barrier injury laboratory-confirmed bloodstream infection criteria. The 14- and 30-day all-cause mortality rates were 13.5% and 22.4%, respectively. Independent predictors of 30-day mortality included age ≥50 years (aOR=2.29, p=0.038), severe graft-versus-host disease (aOR=6.06, p=0.003), septic shock (aOR=30.01, p<0.001). The final predictive model, incorporating these three factors along with pneumonia and high-risk hematologic disease, demonstrated optimal discrimination (AUROC 0.79, 95% CI 0.705-0.867) and calibration. A derived risk score stratified patients into low- (<2 points) and high-risk (≥2 points) groups, with markedly different 30-day mortality (11.3% vs. 39.0%, P<0.001). Conclusions:In hematologic patients, EBSIs commonly arise as breakthrough infections despite broad-spectrum antibiotic coverage, most often associated with mucosal barrier injury. Our parsimonious risk score enables early identification of patients at high risk of 30-day mortality to guide timely interventions.

The BCL-2 inhibitor venetoclax has shown promise in acute lymphoblastic leukemia (ALL), but its role in first-line therapy for newly diagnosed (ND) Philadelphia chromosome-negative (Ph⁻) ALL is undefined. In this prospective phase 2 study, 167 adolescents and adults (aged 14-60 years) with ND Ph⁻ ALL received venetoclax combined with pediatric-inspired chemotherapy. The primary endpoint was the rate of measurable residual disease (MRD) negativity by multiparameter flow cytometry (MFC) after induction. The complete remission rate was 91.0%, and 73.0% of responders achieved MFC-MRD negativity, meeting the primary endpoint. After a median follow-up of 19.3 months, median overall and disease-free survival were not reached; estimated 2-year survival rates were 78.5% and 76.7%, respectively. Propensity score-matched analysis confirmed superior survival compared with historical chemotherapy-only controls. Grade ≥ 3 adverse events were primarily hematologic toxicities and infections, with an incidence comparable to that of the historical cohort. These results demonstrate that adding venetoclax to pediatric-inspired chemotherapy significantly improves MRD response and survival outcomes in ND Ph⁻ ALL, with a manageable safety profile. This trial was registered with ClinicalTrials.gov under the identifier NCT05660473.

Acute leukemias of ambiguous lineage (ALAL) is a rare type of hematologic malignancies with poor outcomes. Currently, the treatment for this type of leukemia lack standardized protocols and exhibit significant heterogeneity, necessitating the exploration of novel, targeted approaches. We retrospectively analyzed the clinical characteristics, efficacy, and safety of 13 newly diagnosed Philadelphia chromosome (Ph)-negative ALAL patients between May 2022 and March 2025, who received induction therapy with the mini-CVD regimen (cyclophosphamide, vincristine, dexamethasone) combined with venetoclax and azacitidine. The cohort comprised 8 males and 5 females, with a median age of 53 years (range, 28–73 years). Among this cohort, 92.3

Daunorubicin dose optimization remains crucial for AML treatment. While 90 mg/m2 benefits younger adults and 45 mg/m2 remains standard for older patients, the optimal dose for patients aged 55-65 years is unclear. We evaluated whether intermediate dose escalation to 60 mg/m2 would improve outcomes compared to that of standard 45 mg/m2 in this population. In this prospective, randomized, open-label, single-center trial, newly diagnosed AML patients aged 55-65 years were randomly assigned 1:1 to receive daunorubicin 45 mg/m2 (Group S) or 60 mg/m2 (Group M) on days 1-3, combined with cytarabine for the induction. At median follow-up of 35.9 months, no significant difference in OS was observed between the two groups (HR 1.24, 95% CI 0.80-1.91; p = 0.333). Median OS was 48.7 months (95% CI 28.2-NR) in Group S vs. 33.0 months (95% CI 22.2-71.6) in Group M. Five-year survival rates were comparable (45.2% vs. 39.8%). CR rates after first induction were equivalent (47.1% vs. 44.4%; RD +2.7%, 95% CI -17.4 to 12.0; p = 0.720). MRD-negative CR rates showed no difference (35.6% vs. 32.2%; p = 0.632). RFS (HR 1.38, 95% CI 0.84-2.26; p = 0.201) and EFS (HR 1.18, 95% CI 0.81-1.74; p = 0.389) were similar in both arms. Regarding safety, while overall infection rates were similar, Group M showed a significantly higher incidence of documented intestinal infections compared to Group S (22.5% vs. 8.0%; p = 0.011). Exploratory subgroup analyses revealed no consistent patterns favoring either strategy across clinical or molecular subgroups. Daunorubicin dose escalation from 45 to 60 mg/m2 provides no clinical benefit but significantly increases mucosal toxicity. Therefore, 45 mg/m2 should remain the preferred regimen for this population. Trial Registration: ClinicalTrials.gov identifier: NCT02432872.

BACKGROUND:KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment. METHODS:In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring KMT2A rearrangements were analyzed. We used FISH, RT-PCR, and next-generation sequencing, including transcriptome and targeted panels, for diagnosis and mutation profiling. All patients received intensive chemotherapy. We evaluated overall survival and event-free survival using Kaplan-Meier and Cox regression models, with HSCT analyzed as a time-dependent variable. RESULTS:The incidence of KMT2A-rearranged AML in our newly diagnosed cohort was 5.9%. Among the 181 patients included in the final analysis, 89 (49.2%) were male and 92 (50.8%) were female, with a median age of 33 years (range: 13-65). The distribution of fusion partners included KMT2A::MLLT3 (n = 39), KMT2A::AFDN (n = 27), KMT2A::MLLT10 (n = 25), KMT2A::ELL (n = 24), and others (n = 12). Seventy-four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). The median follow-up for survivors was 17.53 months (range 1.47-112.57), and the 3-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 42.0% and 32.1%, respectively. Patients with KMT2A::ELL exhibited superior OS compared to other subtypes (3-year OS [ELL vs. non-ELL]: 59.8% vs. 39.3%, p = 0.023). Concomitant mutations did not significantly impact the prognosis of KMT2A-rearranged AML patients. In multivariate analysis, age and HSCT in CR1 were independently associated with OS and EFS (OS: HR = 1.022, p = 0.026 [age]; HR = 0.238, p < 0.001 [HSCT]; EFS: HR = 1.027, p = 0.002 [age]; HR = 0.155, p < 0.001 [HSCT]). Patients aged over 20 years were more likely to benefit from HSCT than those aged 20 years or younger (p < 0.001 [age > 20], p = 0.780 [age ≤ 20]). CONCLUSIONS:Our study revealed the heterogeneous outcomes of KMT2A-rearranged AML patients and clarified the impact of HSCT across different age groups.

While venetoclax (VEN) combined with intensive chemotherapy (IC) has demonstrated efficacy in newly diagnosed acute myeloid leukemia (AML), the optimal duration of VEN administration remains uncertain, leading to variability in its application during induction therapy. Herein, we reported the data of 259 ND AML patients who received 7-day VEN combined with dose-adjusted IC (DA, HAA, or HAD) as induction treatment, to further validate the efficacy and explore the safety of this combination. This study evaluated a truncated 7-day VEN regimen combined with dose-adjusted IC (DA, HAA, or HAD) as induction therapy. The patients included in this study were derived from 2 clinical trials (VEN+DA: ChiCTR2200061524; VEN+HAA: NCT05893472) and 1 retrospective study (VEN+HAD). All induction regimens include a 7-day oral administration of VEN, in combination with either DA, HAA, or HAD regimen. The composite complete remission rate was 90.3%, with a minimal residual disease (MRD) negativity rate of 92.2% as assessed by flow cytometry. After a median follow-up of 18 months, the median overall survival and event-free survival (EFS) were not reached. The estimated 24-month OS, EFS, and relapse-free survival (RFS) rates for the entire cohort were 72.9%, 69.3%, and 70.2%, respectively. No significant differences in survival outcomes were observed among the 3 treatment regimens (OS: P = .68; EFS: P = .73; RFS: P = .34). The median time of the absolute neutrophil count recovered to≥ 0.5 × 109/L and the platelet count to≥ 30 × 109/L after induction therapy was 14 (range: 5-52) days and 13 (range: 4-63) days, respectively. In conclusion, a 7-day VEN schedule maintains high efficacy while potentially reducing myelosuppressive risks of longer regimens.

Inappropriate empirical antimicrobial therapy (IEAT) significantly increases mortality in patients with resistant Gram-negative bacteremia. We developed a multitask machine learning framework to predict carbapenem resistance (CR), β-lactam/β-lactamase inhibitor combinations resistance (BL/BLI-R), and third-/fourth-generation cephalosporins resistance (3GC/4GC-R) in HM patients with monomicrobial BSIs caused specifically by Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae. Using retrospective data from 1,353 HM patients with three specific Enterobacterales BSIs (2017–2023), we trained support vector machines, eXtreme Gradient Boosting, and logistic regression models through 5-fold cross-validation with hyperparameter tuning and conducting internal validation via bootstrap. Model thresholds were optimized via Pareto front analysis to minimized IEAT and carbapenem use while maximizing sensitivity. The models achieved AUCs of 0.81 (95

To investigate the clinical features and outcomes of measurable residual disease recurrence (MRD-R) by multiparameter flow cytometric in acute myeloid leukemia (AML). We retrospectively analyzed clinical characteristic, residual disease status and outcomes of 767 newly diagnosed AML patients achieving complete remission within two cycles of induction at our center. Totally, 171 (22.3%) patients experienced MRD-R during follow-up. Patients with MRD-R had inferior outcomes compared to those without MRD-R, with 3-year cumulative incidence of morphologic relapse (CIR), relapse-free survival (RFS) and overall survival (OS) at 63.6% vs. 30.6% (P

Abstract Objective: To evaluate the efficacy and safety of the triple-combination therapy consisting of all-trans retinoic acid (ATRA), arsenic trioxide (ATO)/realgar-indigo naturalis formula (RIF), and venetoclax in adult patients with acute promyelocytic leukemia (APL). Methods: From February 2025 to July 2025, twenty-six adult APL patients admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, received induction therapy with ATRA+ATO/RIF+venetoclax. The treatment regimen included ATRA (30 mg/m²/day for 4–6 weeks), ATO (0.15 mg/kg/day intravenous infusion) or RIF (60 mg/kg/day orally) total for 4-6weeks, and venetoclax (72 hours after oral administration of ATRA, starting at 100 mg/d on first day and escalating to 200 mg/d for 1 week in low-risk group, 400 mg/d for 1 week in high-risk group). After achieving remission with induction therapy, the low-risk group received two courses of consolidation chemotherapy (ATRA 2 weeks on/2 weeks off, RIF 3 weeks on/1 week off, Venetoclax 200mg 1 week on/3 weeks off. The high-risk group received 3 cycles (Venetoclax 400mg 1 week on/3 weeks off, ATRA and RIF were same as the low-risk group). The primary endpoint was complete remission (CR) rates. We also analyzed the time to correction of coagulopathy the incidence of differentiation syndrome (DS). Diagnosis of DS was made according to the presence of the following signs and symptoms described by Frankel et al. Meeting at least two criteria: dyspnoea, unexplained fever, weight gain greaterthan 5 kg, unexplained hypotension, acute renal failure, and a chest radiograph demonstrating pulmonary infiltrates or pleuropericardial effusion. Results: The cohort comprised 26 patients, stratified into low-risk (n=23) and high-risk (n=3) groups. Baseline characteristics revealed a median age of 48 (range: 36-56) years old with the following hematologic parameters: median WBC count 2.2(range: 0.9-6.3)×10⁹/L, hemoglobin 87 (range: 70-109) g/L, and platelet count 20 (range: 10-40)×10⁹/L. During induction chemotherapy, the peak in leucocyte count was reached in the vast majority of cases within the first week from diagnosis, with only a minority of patients presenting it in the second or third week. The median time to peak leukocyte count was 4 (range: 2–5) days with a median peak leukocyte level of 8.2 (range: 1.6–21.4) ×10⁹/L. One high-risk patient exhibited a progressive leukocyte increase from 35×10⁹/L to 100×10⁹/L, which was subsequently controlled with the addition of cytarabine. The median time to coagulopathy correction was 9 (range: 6–13) days. Treatment-related adverse events including Arsenic-related hepatotoxicity, occurred in 5(19.2%) patients; none of the enrolled patients developed QTc prolongation (defined as absolute value >480 ms) or cardiac adverse events. Beyond these findings, leukocytosis with fever occurred in 4 cases (15.4%), no instances of differentiation syndrome were observed. Additionally, no deaths occurred during the induction phase (within 30 days) with a median hospitalization duration of 14 (range: 11–16) days. After completion of induction chemotherapy, morphologic complete remission (CR) was achieved in all (100%) patients, flow cytometry-based minimal residual disease (MRD) negativity rate was 100%, while complete molecular remission (CMR, PML-RARα negativity by quantitative reverse-transcription PCR) was achieved in 13 (50%) patients. In subsequent follow-up, 21 patients achieved CMR, the median time to achieve CMR was 49 days (range: 42–72). Conclusion: The ATRA + ATO/RIF + venetoclax triple regimen shortened the time to peak leukocyte count and reduced the incidence of differentiation syndrome, compared to previous anthracycline-based combination chemotherapy regimens. The regimen demonstrated rapid hematologic remission and a favorable safety profile in APL induction therapy, showed no significant difference in the median time to achieve CMR. Randomized controlled trials are warranted to validate its potential as a novel first-line treatment option for APL, particularly in high-risk patients. [Keywords]: All-trans retinoic acid; Arsenic trioxide; Venetoclax; Acute promyelocytic leukemia.

To evaluate the efficacy and safety of the HAAV regimen (venetoclax, aclarubicin, cytarabine, homoharringtonine) as induction therapy for newly diagnosed adult acute myeloid leukaemia (AML). This multicentre, single-arm, prospective clinical trial included 84 AML patients (aged 18-60) from eight Chinese hospitals. The HAAV regimen was administered, with venetoclax dosed at 100 mg on day 1, 200 mg on day 2 and 400 mg on days 3-8, combined with homoharringtonine, cytarabine and aclarubicin on days 3-7. The overall response rate after one cycle was 95.2% (95% confidence interval [CI] 88.3-98.7), with 92.9% achieving complete remission + incomplete count recovery (95% CI 83.6-96.6). Among responders, 89.9% (95% CI 80.2-95.8) had minimal residual disease negativity. With a median follow-up of 15.5 months, the -1-year overall survival was 77.9% (95% CI 18.3-26.1), relapse-free survival was 83.9% (95% CI 19.2-22.3) and event-free survival was 71.3% (95% CI 16.9-20.5). The HAAV regimen is highly efficacious and safe for newly diagnosed AML patients.

INTRODUCTION Acute myeloid leukemia (AML) in the high-risk group accounts for about 40-50% of adult acute myeloid leukemia, with a low response rate and poor long-term survival to conventional chemotherapy. In recent years, Venetoclax (VEN) combined with intensive chemotherapy(IC) has significantly improved the complete remission (CR) rate and MRD(-) rate in newly diagnosed AML patients, but the efficacy in patients with high-risk prognosis is still unclear, in order to further explore the efficacy of VEN combined with IC for high-risk AML patients.Herein, we reported the data of 80 patients with newly diagnosed high-risk AML who received 7-day VEN combined with IC (DA, HAA, or HAD) as induction treatment. To further validate the efficacy and safety of VEN combined with IC for AML in high-risk groups. METHODS The patients included in this study were derived from two clinical trials (VEN+DA: ChiCTR2200061524; VEN+HAA: ChiNCT05893472) and one retrospective study (VEN+HAD). All induction regimens include a 7-day oral administration of VEN, in combination with either DA (DNR 60 mg/m²/day d2-3, and Ara-c 100 mg/m²/q12h d2-7), HAA (HHT at 2.5mg/m2/day d3-7, Ara-c 100 mg/m²/day d3-7, and Acla 20mg/day d3-7), or HAD regimen (HHT at 2mg/m2/day d2-6, DNR 45 mg/m²/day d 4-5, and 100 mg/m²/day d2-6). After achieving CR, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) were recommended according to ELN guidelines (2022). Patients who could not proceed allo-HSCT received consolidation and maintenance therapy. The primary objective of this study was to assess the effectiveness and safety of a 7-day VEN-based induction therapy in patients with high-risk AML. The secondary objectives were to evaluate overall survival (OS) and event-free survival (EFS). RESULTS Between January 2023 and June 2024, a total of 80 de novo high-risk patients were enrolled and treated with VEN combined with IC as induction therapy. Among them, 38 patients underwent treatment with VEN+DA, 32 patients received VEN+HAA, and 10 patients were treated with VEN+HAD. The cCR(CR+CRi) rate in the entire cohort was 85.0%(CR 67/80，CRi 1/80), and the MRD(-) rate was 80.0% by flow cytometry. Comparing treatment subgroups, the cCR rates were 86.8% (CR 32/38，CRi 1/38) for VEN+DA, 81.3% (CR 26/32，CRi 0/32) for VEN+HAA, and 90.0%(CR 9/10，CRi 0/10) for VEN+HAD (p=0.722) and MRD negtive rates were 78.9% (30/38), 81.3% (26/32), and 80.0% (8/10), respectively (p=0.972). The most frequent adverse effects were neutropenia (100%), thrombocytopenia (100%) and pneumonia (63.8%). The median recovery time for neutrophils and platelets were 14(range:7-52) and 13(range:4-63) days, respectively. Until April,30, 2025, with a median follow-up of 19(1-38) months, 40.0% of patients underwent allo-HSCT (28.9% in VEN+DA, 40.6% in VEN+HAA, and 80.0% in VEN+HAD, p=0.014). The median OS and EFS were not reached. The estimated 24-month OS and EFS were 60.6% (95% CI: 48.4-72.8%) and 57.8% (95% CI: 46.4-69.2%) in the entire cohort, 55.8% (95% CI: 38.2-73.4%) and 55.2% (95% CI: 38.3-72.1%) in the VEN+DA group, 74.3% (95% CI: 58.8-89.8%) and 68.2% (95% CI: 51.9-84.5%) in the VEN+HAA group, and 38.1% (95% CI: 0.9-75.3%) and 35.0% (95% CI: 3.6-66.4%) in the VEN+HAD group, respectively(OS: p=0.37; EFS: p=0.41). Conclusion 7-day VEN combined with intensive chemotherapy is an effective and safe induction therapy for high-risk AML patients. 【Keywords】Venetoclax; Chemotherapy; AML; Induction treatment；High-risk

Abstract Introduction: Inaticabtagene autoleucel (Inati-cel), featuring a CD19 scFv derived from the HI19a clone and a 4-1BB/CD3-ζ costimulatory domain, was approved in China for adult patients with r/r B-ALL and demonstrated high MRD-negative CR/CRi rate (85.4%) and an estimated 2-year OS rate of 55.2% (Wang Y et al. Blood Adv. 2025). Here, we report the real-world outcomes with more patients and key subgroups described. Methods: The multi-center real-world study (NCT06450067) was conducted from 2023. The endpoints included overall remission rate (ORR), minimal residual disease (MRD) negativity rate, overall survival (OS), relapse-free survival (RFS) and other relevant measures. Both OS and RFS were calculated from the day of Inati-cel infusion. Results: From November 20, 2023, to July 22, 2025, 210 patients underwent leukapheresis, with 156 receiving Inati-cel and 145 included in efficacy and safety analyses. Fifty-four patients underwent apheresis but did not receive the infusion due to manufacture failure (4 pts: 1 for insufficient lymphocytes in the apheresis product, 1 for low CD4/CD8 ratio, and 2 for unknown reasons) or infection (2 pts), or still waiting for infusion. The median age was 39 years (range, 13-76), with 28 patients aged≥60 years. Patients were pretreated with a median of 1 prior lines of therapy (range 1-5). Prior immunotherapies included: HSCT (21.4%), inotuzumab ozogamicin (18.6%), and blinatumomab (28.3%). There were 81 (55.9%) R/R ALL patients:15 (10.3%) primary refractory and 26 (17.9%) with extramedullary lesions, and 64 (44.1%) in CR1 (12 MRD-positive and 52 MRD-negative). About 50% carried high-risk genetic abnormity such as TP53 deletion or mutation (7.6%), MLL rearrangement (9.7%), alterations of IKZF1 (16.6%), Ph-like (4.8%), alterations of PAX5 (5.5%). The median infusion dose was 0.60 (range: 0.42-1.14) ×108CAR-T live cells, with 88% of patients receiving bridge therapy. With a median follow-up of 6.18 months (range: 0.85–19.13months), the BOR in all patients was 92.4% (134/145), and among the cases with remission, the MRD negativity rate was 97.8%. In R/R ALL caess, the BOR and MRD negativity rate were 86.4% (70/81) and 97.1%, respectively. Among the 12 patients with MRD-positive, the MRD-negativity rate reached 100%. Of the 26 patients with extramedullary disease, the ORR was 80%; notably of the 16 patients with CNSL, 15 attained CR. Of the 71 patients with available MRD results assessed by q-PCR or NGS for IG rearrangement after Inati-cel, 87.3% achieved MRD negative. Following infusion, expansion of Inati-cel was observed, even in patients with MRD-negative CR prior to infusion, with peaking around day 14. The longest detectability lasted up to 15 months post-infusion in a patient maintaining CR. The median OS, RFS and DOR have not been reached. The estimated 1-year OS, RFS and DOR rates were 89.3%, 78.1% and 84.7%, respectively. Seven proceeded to allo-HSCT following Inati-cel. Among all responsed patients no significant differences were observed in OS and RFS (P = 0.59 and 0.60, respectively) regardless of the subsequent transplant status, however, significant difference in RFS was observed between patients with subsequent anti-tumor treatment and those without (P = 0.003). Thirteen relapses were observed, with 6 CD19-positive, 6 CD19-negative, and 1 with unknown CD19 status. In the univariate analysis, the number of prior treatment lines, age, previous exposure to blinatumomab, or inotuzumab ozogamicin, and prior history of HSCT were not identified as significant prognostic factors for RFS and OS. A total of 9 patients died: 5 died from disease progression, 2 from transplant-related complications, 1 from infection, and 1 from unknown causes. The most common adverse events (AEs) of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICAN were 53.8% and 4.9%, respectively, while grade ≥3 CRS and ICANS occurring in 2.8% and 2.8%, respectively. All patients recovered without sequelae, with 38 treated with corticosteroids, and 33 with tocilizumab or siltuximab. Conclusion: Real-world data on Inati-cel corroborates its robust response rate, favorable toxicity profile, and survival benefits. Inati-cel demonstrates efficacy in patients with active extramedullary diseases, particularly those with CNSL. In vivo expansion was observed across different disease states.

Background: Adult acute B-cell lymphocytic leukemia (B-ALL) exhibits significant prognostic heterogeneity. The complete remission (CR) rate of traditional induction chemotherapy is 70%-90%. Achieving measurable residual disease (MRD) negativity is a particularly important factor influencing long-term survival outcomes. Nevertheless, treatment-related toxicities are associated with conventional chemotherapy limit the advance in efficacy. Inotuzumab ozogamicin (INO), as an anti-CD22 antibody-drug conjugate, demonstrates potent efficacy and results in less myelosuppression used by dose escalation. Objective: To further explore and optimize the induction strategies, we designed fixed-dose INO combines with vincristine and prednisone (VP) as a new regimen for newly diagnosed B-ALL. Methods: In this multi-center, single-arm, prospective study, patients with newly diagnosed philadelphia chromosome positive (Ph+) or negative (Ph-) B-ALL were enrolled since May 2023. The study had registered in the Chinese Clinical Trial Register (ChiCTR), number ChiCTR2500104832 (Ph+) / ChiCTR2500105597 (Ph-). Both groups (Ph- or Ph+) received INO combined with VP as induction therapy. INO was administered at a fixed-dose of 1 mg on days 1, 8, and 15, capped at a maximum cumulative dose of 2.7 mg/m2. Vincristine was given at 1.4 mg/m² (up to a maximum of 4 mg) on days 1, 8, 15, and 22. Prednisone was administered orally in two patterns: 1 mg/kg daily from days 1 to 14, then 0.5 mg/kg daily from days 15 to 28, or 1 mg/kg on the first 4-days of each week for consecutive four weeks. For Ph+ patients, TKIs were added orally. Patients with peripheral blood leukocyte counts ≥ 25×10⁹/L were eligible for the preparative regimen. Patients received consolidation and maintenance therapy after CR. The primary endpoint was overall response rate (ORR) which includes CR and CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR), MRD negativity rate and safety as the secondary endpoint. Result: By mid-June 2025, a total of twenty-two newly diagnosed B-ALL patients were recruited, included thirteen Ph- B-ALL and nine Ph+ B-ALL, with an ORR of 95.45% (21/22, 95% CI, 87%-100%), and flow MRD negativity of 86.36% (19/22, 95% CI, 72%-100%). All patients acquired remission both estimated CR, the MRD negativity rate was 90.48% (19/21, 95% CI, 78%-100%) among those achieved CR. Baseline characteristics and treatment response are detailed in the subgroups. In the group of Ph- B-ALL, the median age was 56 (17-75) years old, the average peripheral blood leukocyte counts at diagnosed was 15.14 (2.08-33.14) × 109/L, and median bone marrow blast was 85% (38%-96%). The CR rate of this group was 92.31% (12/13, 95%CI, 78%-100%), all these patients achieved CR both showed MRD negativity. Only one patient with IKZF1 mutation was evaluated as non-remission (NR), the NR rate was 7.69% (1/13, 95%CI, 0-22%). In the group of Ph+ B-ALL, the median age was 45 (17-74) years old, average peripheral blood leukocyte counts was 61.32 (1.9-313.79) ×109/L at diagnosed, median bone marrow blast was 87.5% (79%-96%). Six patients carried the BCR-ABL (p190) fusion gene, while three had BCR-ABL (p210). All of them accepted TKIs, four with imatinib, one with dasatinib and four with flumatinib. All the nine patients achieved CR, with a CR rate of 100% (9/9). Seven achieved MRD negativity by flow cytometry, the MRD negative rate was 77.78% (7/9, 95%CI, 50%-100%). Complex karyotype and NRAS mutations may be associated with a higher risk of MRD positivity. During the follow-up treatment, Grade 3-4 hematological toxicity rarely occurred. The median duration of granulocytopenia was 0 (0-7) day and 11 (0-12) days, respectively for Ph- and Ph+ B-ALL. Only 7.69% (1/13) of Ph- B-ALL patients and 22.22% (2/9) of Ph+ B-ALL patients required platelet transfusion. Sinusoidal obstruction syndrome/venoocclusive disease (SOS/VOD) was observed in just one patient. No deaths due to pulmonary infections. Conclusions: The fixed-dose INO combined with VP regimen can be regarded as a highly effective and low-toxicity induction therapy for newly diagnosed patients for both Ph- B-ALL and Ph+ B-ALL.